[unreadable] Ischemic heart disease is a serious health problem and one of the leading causes of death in the United States (American Heart Association 2000). It is also the most important cause of congestive heart failure that debilitates a large number of the elderly population. It is well established that the subendocardium is more vulnerable to ischemic damage than the midmyocardium or the subepicardium. Therefore, an early non-invasive in vivo diagnosis of subendocardium ischemia and the ability to monitor the effects of therapeutic intervention is of significant clinical importance. This proposal will investigate whether nonrigid motion compensation and accurate estimation of myocardial surfaces will enable resolution of subendocardial and subepicardial differences in cardiac PET. Although current whole-body PET scanners have spatial resolution of roughly half the thickness of the myocardial wall, blurring due to respiration and the cardiac contraction have thus far prevented resolution of transmural differences. This proposal builds on encouraging results of prior respiratory and contractile motion compensation work. Algorithms will be developed that accurately model the elastic properties of the heart, enforce temporal smoothness and compensate for partial volume effects in order to reduce the blurring effects of cardiac contractile motion. The proposed research will also develop new methods to combine early blood pool data with late uptake data in dynamic cardiac PET so that endocardial and epicardial surface detection can be improved, even in the presence of tracer uptake defects. New algorithm development will be evaluated using data from mathematical phantom and animal experiments, both of which will provide gold standard comparisons as an end point. The experiments will allow determination of whether currently available whole-body PET scanners can resolve transmural uptake differences and thus better answer questions regarding the etiology of the stunned and hibernating myocardium. [unreadable] [unreadable]